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J. Biol. Chem., Vol. 276, Issue 48, 45225-45235, November 30, 2001
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From the Department of Chemistry and Biochemistry, University of
California, San Diego, La Jolla, California 92093-0359
NF-
I
B
, but Not IB
, Functions as a Classical Cytoplasmic
Inhibitor of NF-B Dimers by Masking Both NF-B Nuclear
Localization Sequences in Resting Cells*
,
B dimers, inhibitor IB proteins, and
NF-B·IB complexes exhibit distinct patterns in
partitioning between nuclear and cytoplasmic cellular compartments.
IB-dependent modulation of NF-B subcellular
localization represents one of the more poorly understood processes in
the NF-B signaling pathway. In this study, we have combined in
vitro biochemical and cell-based methods to elucidate differences
in NF-B regulation exhibited by the inhibitors IB
and
IB
. We show that although both IB and IB bind to NF-B with similar global architecture and stability, significant differences exist that contribute to their unique functional roles. IB derives its high affinity toward NF-B dimers by binding to
both NF-B subunit nuclear localization signals. In contrast, IB contacts only one NF-B NLS and employs its
carboxyl-terminal proline, glutamic acid, serine, and threonine-rich
region for high affinity NF-B binding. We show that the presence of
one free NLS in the NF-B·IB complex renders it a dynamic
nucleocytoplasmic complex, whereas NF-B·IB complexes are
localized to the cytoplasm of resting cells.
*
This work was supported by NCI, National Institutes of
Health, Grant CA-78749 and by Alfred P. Sloan and Hellman fellowships (to G. G.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Aurora Biosciences Corp., 11010 Torreyana Rd.,
San Diego, CA 92121.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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